{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T22:57:46Z","timestamp":1778972266681,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1621,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Summary: Iterative similarity searches with PSI-BLAST position-specific score matrices (PSSMs) find many more homologs than single searches, but PSSMs can be contaminated when homologous alignments are extended into unrelated protein domains\u2014homologous over-extension (HOE). PSI-Search combines an optimal Smith\u2013Waterman local alignment sequence search, using SSEARCH, with the PSI-BLAST profile construction strategy. An optional sequence boundary-masking procedure, which prevents alignments from being extended after they are initially included, can reduce HOE errors in the PSSM profile. Preventing HOE improves selectivity for both PSI-BLAST and PSI-Search, but PSI-Search has ~4-fold better selectivity than PSI-BLAST and similar sensitivity at 50% and 60% family coverage. PSI-Search is also produces 2- for 4-fold fewer false-positives than JackHMMER, but is ~5% less sensitive.<\/jats:p>\n               <jats:p>Availability and implementation: PSI-Search is available from the authors as a standalone implementation written in Perl for Linux-compatible platforms. It is also available through a web interface (www.ebi.ac.uk\/Tools\/sss\/psisearch) and SOAP and REST Web Services (www.ebi.ac.uk\/Tools\/webservices).<\/jats:p>\n               <jats:p>Contact: \u00a0pearson@virginia.edu; rodrigo.lopez@ebi.ac.uk<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts240","type":"journal-article","created":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T01:38:05Z","timestamp":1335490685000},"page":"1650-1651","source":"Crossref","is-referenced-by-count":30,"title":["PSI-Search: iterative HOE-reduced profile SSEARCH searching"],"prefix":"10.1093","volume":"28","author":[{"given":"Weizhong","family":"Li","sequence":"first","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamish","family":"McWilliam","sequence":"additional","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mickael","family":"Goujon","sequence":"additional","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Cowley","sequence":"additional","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Lopez","sequence":"additional","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Pearson","sequence":"additional","affiliation":[{"name":"1 EMBL \u2013 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK and 2Department of Biochemistry and Molecular Genetics, Charlottesville, VA 22908, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,4,25]]},"reference":[{"key":"2023012512324678800_B1","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1093\/bioinformatics\/btp089","article-title":"PSIBLAST_PairwiseStatSig: reordering PSI-BLAST hits using pairwise statistical significance","volume":"25","author":"Agrawal","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012512324678800_B2","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2023012512324678800_B3","doi-asserted-by":"crossref","first-page":"5101","DOI":"10.1111\/j.1742-4658.2005.04945.x","article-title":"Protein database searches using compositionally adjusted substitution matrices","volume":"272","author":"Altschul","year":"2005","journal-title":"FEBS J."},{"key":"2023012512324678800_B4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/nar\/gkn981","article-title":"PSI-BLAST pseudocounts and the minimum description length principle","volume":"37","author":"Altschul","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012512324678800_B5","doi-asserted-by":"crossref","first-page":"W143","DOI":"10.1093\/nar\/gkl157","article-title":"Cascade PSI-BLAST web server: a remote homology search tool for relating protein domains","volume":"34","author":"Bhadra","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2023012512324678800_B6","doi-asserted-by":"crossref","first-page":"e1002195","DOI":"10.1371\/journal.pcbi.1002195","article-title":"Accelerated profile HMM searches","volume":"7","author":"Eddy","year":"2011","journal-title":"PLoS Comput. 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